Prenatal substance use is associated with a number of neonatal consequences, including low birthweight and increased mortality. Some women spontaneously quit substance use on learning they are pregnant. Others continue substance use throughout pregnancy, thus increasing risk of medical and developmental problems in their infants. Better interventions are needed to enhance medical and developmental problems in their infants. Better interventions are needed to enhance prenatal substance use quit rates. Currently the most widely used strategy is brief professional advice (BPA), which has only limited clinical effectiveness. The proposed research will conduct a random-assignment clinical trial to assess effectiveness of three interventions of increasing clinical intensity on reducing prenatal substance use. Subjects will be pregnant women enrolled in a hospital obstetrical clinic (estimated gestational age less than twenty-eight weeks). They will be selected from patients reporting alcohol, tobacco, or illicit drug use during the past thirty days or testing positive for such use on toxicological screens at the time of the first prenatal visit. One group of subjects (N=270) will receive BPA only, which is standard medical practice. A second group (N=270) will receive BPA in combination with behavioral incentives (BI). A third group (N=270) will receive BPA and BI in combination with Motivational Enhancement Therapy (MET). Effects of the interventions will be evaluated on both clinical and economic measures. The study will also collect epidemiological data to identify factors (including depression, family history, level of dependence) associated with quitting of prenatal alcohol, tobacco, and illicit drug use. Results from subjects with prenatal substance use will be compared to community-based controls without prenatal substance use (N=270). Possible interactions between prenatal substance use will also be investigated. Subjects will be followed from the first prenatal visit to three mo post partum, employing self-report, toxicological, and collateral-report measures of substance use. The subjects will be lower socioeconomic status urban women with a high school or less education with high rates of prenatal substance use.